Reply:
Authors: Subrat Kumar Acharya
Journal: Hepatology (2010)

The data reported by Devarbhavi et al. in their letter on antitubercular therapy (ATT)–induced acute liver failure (ALF) are indeed similar to the figures reported by us.1 These patients had a high mortality rate (67% in both reports) and were young (mean ages of 32 and 40 years), and most of the patients in both reports underwent, without definite evidence of tuberculosis, antitubercular treatment that could have been avoided (63% and 42%). Devarbhavi et al. suggested that there are other causes of drug-induced liver injury (DILI) and DILI-ALF in India. To support this statement, they provided their data on DILI: approximately 60% of all DILI cases and approximately 77% (three-fourths) of DILI-ALF cases were due to ATT. Therefore, in India, ATT is the most important drug implicated in DILI. The collated data on consecutive patients with ALF reported from Kashmere,2 central India,3 and north India4, 5 by other Indian authors also show that ATT-induced ALF was the sole cause of DILI-ALF in their series. The All India Institute of Medical Sciences is a major referral center in north India, particularly for ALF, and we evaluated 1223 consecutive patients with ALF from 1986 to 2009; surprisingly, we have not been able to document paracetamol or other drugs or indigenous medicine as a cause of ALF in these patients.1 These reports indicate that ATT is indeed the major cause of DILI in India. As indicated by Devarbhavi et al., other drugs may cause DILI, but the frequency is very low. During a 10-year period (1997-2008), Devarbhavi et al. documented that 76.6% of DILI-ALF cases were due to ATT, and 15 patients had ALF due to other drugs. The authors have not provided the exact number of ALF patients. However, when we reanalyzed this figure, we found that probably there were 64 patients with DILI-ALF, and for 49, DILI-ALF was due to ATT; this indicates that ATT is the most important cause of DILI in India. Paracetamol, which is the most frequent cause of DILI-ALF in the United Kingdom and United States, was documented in only one patient in Devarbhavi et al.'s report over a 10-year period. The cultural practices in the West and East are different. Paracetamol is a drug sold over the counter in the West and is available in almost all households; therefore, people have easy access to this drug for suicide, and on rare occasions, accidental consumption causing ALF has also been reported. In the households of India, an agriculture-based country, organophosphorous compounds used as pesticides are readily available and are consumed for the purpose of suicide. Furthermore, Indians are a distinct race and may have different genetic drug-metabolizing capabilities, about which information is lacking. Therefore, even though DILI-ALF due to agents other than ATT may occur in this country, as indicated by Devarbhavi et al., the frequency is probably very low; this is also supported by multiple reports on ALF from India.2-5 The other issue raised by Devarbhavi et al. is that, despite an increase in the prevalence of acquired immune deficiency syndrome (AIDS) and tuberculosis, in our study, the frequency of ATT-induced ALF was reported to be less during the last decade (1998-2009) than the frequency of ATT-induced ALF in the previous decade (1986-1997). Seventy-four percent of our patients with ATT-induced ALF (52/70) were documented from 1986 to 1997, whereas 26% (18/70) were diagnosed from 1998 to 2009.1 Devarbhavi et al. suggested that because of increases in the frequency of AIDS and consequently tuberculosis, an increase in the number of ATT-induced ALF cases would be expected. However, an increase in the frequency of AIDS and tuberculosis would not necessarily lead to an increase in the number of ATT-induced DILI cases. There is no evidence to date that an increase in the frequency of AIDS and tuberculosis would increase ATT-induced toxicity. Even Devarbhavi et al. have not been able to provide any data showing an increase in ATT-induced ALF in their series during the last decade, and no information on the human immunodeficiency virus (HIV) status is available either. However, none of our ATT-induced ALF cases had HIV. During the last decade in India, antitubercular treatment has been administered through the DOTS (Directly Observed Treatment, Short-Course) program, in which ATT is administered to patients under supervision. In such a situation, the empirical use of ATT is likely to be less frequent, and this may explain the lower frequency of ATT-induced ALF during the last decade in our report. Subrat Kumar Acharya*, * Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.